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PMID:16109376
| Citation |
Jang, MK, Mochizuki, K, Zhou, M, Jeong, HS, Brady, JN and Ozato, K (2005) The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol. Cell 19:523-34 |
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| Abstract |
Brd4 is a mammalian bromodomain protein that binds to acetylated chromatin. Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that constitutes core positive transcription elongation factor b (P-TEFb). Brd4 interacted with P-TEFb in the living nucleus through its bromodomain. About half of P-TEFb was bound to the inhibitory subunit and functionally inactive. Brd4 interacted with P-TEFb that was free of the inhibitory subunit. An increase in Brd4 expression led to increased P-TEFb-dependent phosphorylation of RNA polymerase II (RNAPII) CTD and stimulation of transcription from promoters in vivo. Conversely, a reduction in Brd4 expression by siRNA reduced CTD phosphorylation and transcription, revealing that Brd4 is a positive regulatory component of P-TEFb. In chromatin immunoprecipitation (ChIP) assays, the recruitment of P-TEFb to a promoter was dependent on Brd4 and was enhanced by an increase in chromatin acetylation. Together, P-TEFb alternately interacts with Brd4 and the inhibitory subunit to maintain functional equilibrium in the cell. |
| Links |
PubMed Online version:10.1016/j.molcel.2005.06.027 |
| Keywords |
Animals; Cyclin-Dependent Kinase 9/genetics; Cyclin-Dependent Kinase 9/metabolism; DNA, Complementary/metabolism; Mice; Nuclear Proteins; Oncogene Proteins, Fusion/genetics; Oncogene Proteins, Fusion/physiology; Positive Transcriptional Elongation Factor B/metabolism; Promoter Regions, Genetic; RNA Polymerase II/genetics; RNA Polymerase II/metabolism; RNA, Small Nuclear/genetics; RNA, Small Nuclear/metabolism; Transcription Factors; Transcription, Genetic/physiology |
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Significance
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